More than four years of durable transfusion
independence (TI), stable total hemoglobin (Hb) levels and reduced
liver iron concentrations in completed Phase 1/2 Northstar
(HGB-204) study in patients who do not have a β0/β0 genotype
Ninety percent of evaluable patients who do not
have a β0/β0 genotype achieved TI, with median average total Hb
levels of 12.2 g/dL in Phase 3 Northstar-2 (HGB-207) study
In ongoing Phase 3 Northstar-3 (HGB-212) study
in patients with β0/β0 genotype or IVS-I-110 mutation, the two
patients evaluable for TI achieved it with Hb levels of 13.2 g/dL
and 10.4 g/dL at last visit
Nine of 11 patients with at least six months of
follow-up in HGB-212 have not had a transfusion for at least three
months
bluebird bio, Inc. (Nasdaq: BLUE) announced new data from
ongoing studies of LentiGlobin™ gene therapy for β-thalassemia
(betibeglogene autotemcel) in pediatric, adolescent and adult
patients who have transfusion-dependent β-thalassemia (TDT),
including results from the Phase 3 Northstar-3 (HGB-212) study in
patients with a β0/β0 genotype or IVS-I-110 mutation, and the Phase
3 Northstar-2 (HGB-207) study in patients who do not have a β0/β0
genotype. These data, as well as updated results reflecting up to
five years of follow-up from the completed Phase 1/2 Northstar
(HGB-204) study, were presented at the 61st American Society of
Hematology (ASH) Annual Meeting and Exposition in Orlando,
Florida.
As of the data cutoff presented today, 52 pediatric, adolescent
and adult patients with TDT who do not have a β0/β0 genotype or
have a β0/β0 genotype have been treated with LentiGlobin for
β-thalassemia in the Northstar, Northstar-2 and Northstar-3
studies.
“The results from our clinical studies of LentiGlobin for
β-thalassemia support its potential benefits and consistent safety
profile across a broad range of TDT genotypes and patient
populations, including pediatric patients, with the longest
duration of follow-up now extending beyond five years,” said David
Davidson, M.D., chief medical officer, bluebird bio. “Importantly,
patients have achieved and maintained transfusion independence,
with improvements in multiple markers of bone marrow red blood cell
production, as well as reductions in iron overload. These outcomes
demonstrate the long-term disease-modifying potential of
LentiGlobin for people living with TDT.”
TDT is a severe genetic disease caused by mutations in the
β-globin gene that result in reduced or significantly reduced
hemoglobin (Hb). In order to survive, people with TDT maintain Hb
levels through lifelong chronic blood transfusions. These
transfusions carry the risk of progressive multi-organ damage due
to unavoidable iron overload.
LentiGlobin for β-thalassemia was designed to address the
underlying genetic cause of TDT by adding functional copies of a
modified form of the β-globin gene (βA-T87Q-globin gene) into a
patient’s own hematopoietic (blood) stem cells (HSCs). bluebird
bio’s clinical development program for LentiGlobin for
β-thalassemia includes studies across patient genotypes, including
those who do not have a β0/β0 genotype, as well as those with a
β0/β0 genotype.
“Blood transfusions, while necessary, result in unavoidable iron
overload, which can cause multi-organ damage. These infusions also
have an impact on patients and their families’ lives,” said
Ashutosh Lal, M.D., UCSF Benioff Children’s Hospital, Oakland,
Calif. “It’s encouraging to see that adult, adolescent and
pediatric patients with various genotypes in the LentiGlobin for
β-thalassemia clinical trials have achieved and continue to
maintain transfusion independence.”
Northstar (HGB-204) Efficacy
As of June 12, 2019, data from up to five years (median 44.9;
min–max: 34.8–61.3 months) of follow-up from the completed Phase
1/2 Northstar (HGB-204) study show durable transfusion independence
(TI) and stable HbAT87Q levels in patients who achieved TI. TI is
defined as weighted average Hb ≥ 9 g/dL without red blood cell
(RBC) transfusions for more than 12 months.
Eight of 10 treated patients who did not have a β0/β0 genotype
achieved and continued to maintain TI for up to 51.3 months as of
the data cutoff, with a median weighted average Hb during TI of
10.3 g/dL. Transfusion volumes were reduced by 79% and 52% in the
two patients who did not achieve TI.
In patients who have a β0/β0 genotype (n=8), three of eight
achieved and continued to maintain TI with a current duration up to
30.4 months as of the data cutoff, and a median weighted average Hb
during TI of 9.9 g/dL.
Among patients who achieved TI, a decrease in markers of iron
burden, including liver iron concentration, serum ferritin and
transferrin saturation, were observed over time. Liver iron
concentrations began to decrease in eight of the 11 patients who
achieved TI, with the largest decrease observed in patients who had
48 months of data available (n=7). A median 44% reduction (min–max:
17%–83%) was reported in these seven patients.
Northstar-2 (HGB-207) Efficacy
As of June 12, 2019, 21 of 23 patients were treated and have
been followed for a median of 11.6 months. These patients ranged in
age from 8 to 34 years, including six pediatric (<12 years) and
15 adolescent/adult (≥12 years) patients. Three patients with more
than 24 months of follow-up are enrolled in the long-term follow-up
study LTF-303.
Ninety percent (9/10) of patients evaluable for TI had achieved
it, with median weighted average Hb levels of 12.2 g/dL (min–max:
11.4–12.8 g/dL) during TI. All nine patients continued to maintain
TI for a median duration of 15.2 months (min–max: 12.1–21.3 months)
as of the data cutoff.
Ninety percent (18/20) of patients with at least five months of
follow-up had not received a transfusion for at least 3.5 months
and total Hb was near normal in most, with the median total Hb at
Months 6, 12 and 18 at 11.5 (n=17), 12.3 (n=11) and 12.2 g/dL
(n=8), respectively. HbAT87Q levels were stable over time: 8.7 g/dL
at Month 6; 9.3 g/dL at Month 12; and 9.4 g/dL at Month 18.
In an exploratory analysis, bone marrow from nine patients who
had reached 12 months of follow-up and were transfusion independent
was evaluated for myeloid to erythroid ratio. A low myeloid to
erythroid ratio is a key feature of abnormal bone marrow RBC
production that is characteristic of patients with TDT.
In all nine patients, an increase in the myeloid to erythroid
ratio was observed, suggesting improvement in bone marrow RBC
production. A trend toward normalization of soluble transferrin
receptor, a marker of RBC production, and reticulocyte counts, a
marker of hemolysis or RBC destruction, was also observed. The
trend toward normalization in RBC production supports the
disease-modifying potential of LentiGlobin for β-thalassemia for
patients with TDT.
Northstar-3 (HGB-212) Efficacy
As of September 30, 2019, 13 patients (eight β0/β0, two
β0/IVS-I-110, three homozygous IVS-I-110 genotypes) were treated
and had a median follow-up of 8.8 months (min–max: 2.5–20.0
months). Median age at enrollment was 17 years of age (min–max:
7–33 years); four patients were under 12 years of age.
Two patients had at least 12 months of follow-up and were
evaluable for TI. Both patients, one patient with a β0/β0 genotype
and one pediatric patient with a β0/IVS-I-110 genotype, achieved
TI, and continued to maintain it with Hb levels of 13.2 g/dL and
10.4 g/dL, respectively, at last visit.
In addition, nine of 11 patients with at least six months of
follow-up did not receive a transfusion for more than three months
as of last follow-up. In these patients, total Hb levels ranged
from 8.3–14.2 g/dL at last visit.
LentiGlobin for β-thalassemia Safety
Non-serious adverse events (AEs) observed during the HGB-204,
HGB-207 and HGB-212 clinical studies that were attributed to
LentiGlobin for β-thalassemia were hot flush, dyspnoea, abdominal
pain, pain in extremities, thrombocytopenia, leukopenia,
neutropenia and non-cardiac chest pain. One serious adverse event
(SAE) of thrombocytopenia was considered possibly related to
LentiGlobin for β-thalassemia for TDT.
Additional AEs observed in clinical studies were consistent with
the known side effects of HSC collection and bone marrow ablation
with busulfan, including SAEs of veno-occlusive disease.
With more than five years of follow-up to date, there have been
no new unexpected safety events, no deaths, no graft failure and no
cases of vector-mediated replication competent lentivirus or clonal
dominance. In addition, there have been no new reports of
veno-occlusive liver disease (VOD) as of the data cutoff presented
at ASH.
About LentiGlobin for β-Thalassemia (betibeglogene
autotemcel)
The European Commission granted conditional marketing
authorization for LentiGlobin for β-thalassemia, to be marketed as
ZYNTEGLO™ (autologous CD34+ cells encoding βA-T87Q-globin gene)
gene therapy, for patients 12 years and older with TDT who do not
have a β0/β0 genotype, for whom hematopoietic stem cell (HSC)
transplantation is appropriate, but a human leukocyte antigen
(HLA)-matched related HSC donor is not available.
TDT is a severe genetic disease caused by mutations in the
β-globin gene that result in reduced or significantly reduced
hemoglobin (Hb). In order to survive, people with TDT maintain Hb
levels through lifelong chronic blood transfusions. These
transfusions carry the risk of progressive multi-organ damage due
to unavoidable iron overload.
LentiGlobin for β-thalassemia adds functional copies of a
modified form of the β-globin gene (βA-T87Q-globin gene) into a
patient’s own hematopoietic (blood) stem cells (HSCs). Once a
patient has the βA-T87Q-globin gene, they have the potential to
produce HbAT87Q, which is gene therapy-derived hemoglobin, at
levels that may eliminate or significantly reduce the need for
transfusions.
The conditional marketing authorization for ZYNTEGLO is only
valid in the 28 member states of the EU as well as Iceland,
Liechtenstein and Norway. For details, please see the Summary of
Product Characteristics (SmPC).
The U.S. Food and Drug Administration granted LentiGlobin for
β-thalassemia Orphan Drug status and Breakthrough Therapy
designation for the treatment of TDT.
By the end of 2019, bluebird bio plans to initiate rolling
submission of a Biologics Licensing Application (BLA) of
LentiGlobin for β-thalassemia in the U.S. for the treatment of
patients with TDT who do not have a β0/β0 genotype. bluebird bio is
engaged with the FDA in discussions regarding the requirements and
timing of the various components of the rolling BLA submission and,
subject to these ongoing discussions, the company is currently
planning to complete the BLA submission in the first half of
2020.
LentiGlobin for β-thalassemia continues to be evaluated in the
ongoing Phase 3 Northstar-2 and Northstar-3 studies. For more
information about the ongoing clinical studies, visit
www.northstarclinicalstudies.com or
clinicaltrials.gov and use identifier NCT02906202 for
Northstar-2 (HGB-207), NCT03207009 for Northstar-3 (HGB-212).
bluebird bio is conducting a long-term safety and efficacy
follow-up study (LTF-303) for people who have participated in
bluebird bio-sponsored clinical studies of LentiGlobin for
β-thalassemia. For more information visit:
https://www.bluebirdbio.com/our-science/clinical-trials or
clinicaltrials.gov and use identifier NCT02633943 for LTF-303.
About bluebird bio, Inc.
bluebird bio is pioneering gene therapy with purpose. From our
Cambridge, Mass., headquarters, we’re developing gene therapies for
severe genetic diseases and cancer, with the goal that people
facing potentially fatal conditions with limited treatment options
can live their lives fully. Beyond our labs, we’re working to
positively disrupt the healthcare system to create access,
transparency and education so that gene therapy can become
available to all those who can benefit.
bluebird bio is a human company powered by human stories. We’re
putting our care and expertise to work across a spectrum of
disorders including cerebral adrenoleukodystrophy, sickle cell
disease, β-thalassemia and multiple myeloma, using three gene
therapy technologies: gene addition, cell therapy and
(megaTAL-enabled) gene editing.
bluebird bio has additional nests in Seattle, Wash.; Durham,
N.C.; and Zug, Switzerland. For more information, visit
bluebirdbio.com.
Follow bluebird bio on social media: @bluebirdbio,
LinkedIn, Instagram and YouTube.
ZYNTEGLO, LentiGlobin, and bluebird bio are trademarks of
bluebird bio, Inc.
The full common name for ZYNTEGLO: A genetically modified
autologous CD34+ cell enriched population that contains
hematopoietic stem cells transduced with lentiviral vector encoding
the βA-T87Q-globin gene.
Forward-Looking Statements
This release contains “forward-looking statements” within the
meaning of the Private Securities Litigation Reform Act of 1995,
including statements regarding the Company’s views with respect to
the potential for LentiGlobin to treat transfusion-dependent
β-thalassemia (TDT). Any forward-looking statements are based on
management’s current expectations of future events and are subject
to a number of risks and uncertainties that could cause actual
results to differ materially and adversely from those set forth in
or implied by such forward-looking statements. These risks and
uncertainties include, but are not limited to, the risks that the
preliminary positive efficacy and safety results from our prior and
ongoing clinical trials of LentiGlobin to treat TDT will not
continue or be repeated in our ongoing or planned clinical trials
or in the commercial context, risks that the current or planned
clinical trials of our product candidates will be insufficient to
support future regulatory submissions or to support marketing
approval in the US, the risk that the ability to submit and obtain
approval of a BLA is ultimately an FDA review decision and the FDA
may impose additional requirements before we can submit or obtain
approval of a BLA, or before we are able to treat patients in the
commercial context, and the risk that any one or more of our
product candidates, will not be successfully developed, approved or
commercialized. For a discussion of other risks and uncertainties,
and other important factors, any of which could cause our actual
results to differ from those contained in the forward-looking
statements, see the section entitled “Risk Factors” in our most
recent Form 10-Q, as well as discussions of potential risks,
uncertainties, and other important factors in our subsequent
filings with the Securities and Exchange Commission. All
information in this press release is as of the date of the release,
and bluebird bio undertakes no duty to update this information
unless required by law.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20191209005708/en/
Investors: Elizabeth Pingpank, 617-914-8736
epingpank@bluebirdbio.com or Media: Catherine Falcetti,
617-583-3411 cfalcetti@bluebirdbio.com
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